This proposal is a competing renewal application in response to RFA number HD-98-002 to continue funding of a Pediatric Pharmacology Research Unit at Children's Mercy Hospital (CMH), Kansas City, Missouri as one of the sites within the NICHD Network of PPRU's. The objectives of the Unit are: 1) to continue and expand collaborative participation of the CMH PPRU in the PPRU Network for the primary purpose of producing data that will support labeling of drugs for children; and 2) To conduct basic translational research focusing on regulatory events in pharmacogenetics, ontogeny of important drug metabolizing enzymes and pharmacodynamics that will advance our understanding of age-related differences in drug disposition and action. Specific Aims include: 1) The collaborative conduct of studies of new and currently marketed drugs with priority given to PPRU network studies; 2) The identification, collation, analysis, and interpretation of data from pediatric clinical trials sufficient for expansion of pediatric labeling; 3) Use of molecular approaches to define the "link" between childhood development and drug metabolism; 4) Examination of the interface between pharmacogenetics, the ontogeny of critical drug-metabolizing enzymes, and the pharmacokinetics of drugs; 5) The provision of a unique teaching environment in which pediatricians, medical sub-specialists, clinical pharmacists, nurses and allied health care professionals can gain expertise in the discipline of pediatric clinical pharmacology. The capability of the investigators and applicant institution to accomplish these objectives and specific aims is demonstrated by: 1) effective programmatic composition and administration; 2) expertise and resources within the applicant institution; 3) previous and current research accomplishments related to the PPRU Network; 4) projected programmatic expansion necessary to meet the anticipated increased demands for pediatric clinical trials over the next five years; and 5) presentation of two new research proposals which speak directly to the program objectives and are ideally suited for conduct within the PPRU Network.